Antibody studies show encouraging results in patients with high-risk forms of two types of blood cancer

Antibody studies show encouraging results in patients with high-risk forms of two types of blood cancer

Two clinical trials testing the antibody loncastuximab tesirine (Zynlonta) showed encouraging results in patients with high-risk forms of two types of blood cancer - follicular lymphoma and marginal zone lymphoma. The findings, led by physicians and scientists at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, will be presented at the 2024 American Society of Hematology meeting in San Diego.

In one study, a phase 2 clinical trial led by Dr. According to Dr. Juan Alderuccio, a Sylvester hematologist and lymphoma specialist and associate professor of medicine at the Miller School, loncastuximab was tested in combination with the antibody rituximab in 39 patients with relapsed or refractory follicular lymphoma who also had a high tumor burden. This study will also be published in the journal on December 7thLancet hematology. Alderuccio is now expanding this study, which included all Sylvester patients, to patients at multiple sites across the U.S. and to enroll a total of 100 patients.

The other study, led by Izidore Lossos, MD, professor of medicine and head of the lymphoma section of the Division of Hematology at Sylvester University, tested loncastuximab alone in 23 patients with relapsed or refractory marginal zone lymphoma, a rare form of non-Hodgkin's lymphoma, in an ongoing multicenter phase 2 trial.

Both studies showed encouraging results for the new treatment in these patient groups.

Because both cancers tend to grow slowly, both studies looked at overall response and complete response rates rather than survival rates. In the follicular lymphoma study, patients who received loncastuximab and rituximab had a complete response rate of 67%, meaning their cancer could no longer be detected by imaging, and an overall response rate of 97% - only one of 39 patients did not respond to study treatment. In the marginal zone lymphoma study, 70% of patients had a complete response and 91% had an overall response. Since this process is still ongoing, Lossos will present interim results at the conference.

Overcome high-risk factors

Although both types of lymphoma are typically indolent or slow-growing, patients with both types may experience faster cancer progression and poorer prognoses. For the follicular lymphoma study, Alderuccio and his colleagues recruited patients whose cancer had not only relapsed or failed to respond to treatment, but also had a high disease burden or whose disease had progressed within 24 months of initial treatment and had a worse prognosis. Patients with faster-progressing follicular lymphoma, known as POD24, have a five-year survival rate of just 50%, compared to an 85% survival rate for follicular lymphoma patients overall.

Most positive, the antibody combination showed similar response rates in patients with POD24 and those without POD24, each representing about half of the patients in the study.

Even in patients with high-risk disease, this treatment can overcome adverse prognostic factors.”

Juan Alderuccio, MD, a Sylvester hematologist and lymphoma specialist and associate professor of medicine at the Miller School

In the marginal zone lymphoma study, the complete response rate of 70% was the highest such rate in any study of this cancer, Lossos said. Although this cancer also grows slowly, relapsed patients rarely achieve a complete response in other treatment settings.

Reduce side effects

Alderuccio noted that the treatment landscape for high-risk follicular lymphoma has changed dramatically, especially in the last few years. Patients now have many more treatment options available than before.

“The prognosis for patients with relapsed or refractory follicular lymphoma has improved significantly in recent years,” he said. "We have several options and our goal now is to maintain high efficacy but also reduce toxicity. And that's exactly what we're trying to do now."

Although other treatment options also show high effectiveness, the antibody combination appears to combine this high effectiveness with a low burden of side effects and a short treatment duration. The main side effects observed in the study were a rash that worsened with sun exposure (patients are advised to stay out of the sun during treatment) and fluid retention, which can be treated with diuretics.

Because so many patients showed a complete response after just 12 weeks of treatment, researchers also recently reduced the treatment duration in their study from 10 to 6 months. Alderuccio hopes that patients will be able to undergo this treatment easily due to the relatively short treatment duration and low toxicity. One of the patients who completed treatment in the study was 89 years old.

Options for a rare cancer

The Marginal Zone Lymphoma Study is unique in that most clinical trials do not exclude patients with this type of cancer because it is relatively rare, accounting for only 6 to 8% of non-Hodgkin lymphoma cases. Although other studies have included patients with this cancer, it can be difficult to draw conclusions from these studies because the number of patients with marginal zone lymphoma in each study is so low, Lossos said.

Although it is an indolent disease with a median survival time of 10 to 15 years, many patients require immediate treatment because the cancer can cause significant symptoms such as vision loss. In most patients, the cancer does not go away despite treatment - a complete response has so far been rare with this disease. For this reason, Lossos is optimistic about the 70% complete response rate observed so far in the ongoing trial, which included 23 of 50 planned patients. Currently, sites are open at the University of Miami and City of Hope, and researchers will soon expand that to a total of five sites.

“We are thrilled with the complete response rate,” Lossos said. “We hope that this treatment will allow patients to live much longer than before.”

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